近日出版的《細(xì)胞—代謝》（Cell Metabolism）雜志刊出,，一個(gè)人在節(jié)食的時(shí)候，他的腦細(xì)胞也在節(jié)食,。這些饑餓的腦細(xì)胞會(huì)釋放“我要吃東西”的信號(hào)加速饑餓,，并使新陳代謝放慢，導(dǎo)致減肥前功盡棄。
此項(xiàng)研究的參與者,，紐約市布朗克斯區(qū)的愛(ài)因斯坦醫(yī)學(xué)院的RajatSingh說(shuō)：“我們培育了一批大腦不能發(fā)出饑餓信號(hào)的老鼠,，它們的神經(jīng)元中缺少產(chǎn)生增加食欲的蛋白，研究發(fā)現(xiàn)這些老鼠在挨餓后吃得少了,，更瘦也更健康了,。這些神經(jīng)元能感應(yīng)身體中的營(yíng)養(yǎng)狀況，告訴身體是吃東西還是不要吃東西,。”
由這些神經(jīng)元產(chǎn)生的饑餓機(jī)制和饑餓感通過(guò)一個(gè)叫自噬的過(guò)程發(fā)出信號(hào),。大多數(shù)腦細(xì)胞自噬的時(shí)候都保持穩(wěn)定的水平，不會(huì)對(duì)饑餓有所反應(yīng),。而食欲感應(yīng)神經(jīng)元不同,，它是唯一已知的在饑餓的時(shí)候加強(qiáng)自噬過(guò)程的腦細(xì)胞。加強(qiáng)后的自噬過(guò)程增加了游離脂肪酸的細(xì)胞水平,，而這更高水平的脂肪酸讓這些特別的腦細(xì)胞分子釋放出產(chǎn)生食欲的老鼠基因相關(guān)蛋白,。因?yàn)槔鲜蠡蛳嚓P(guān)蛋白只在食欲控制神經(jīng)元中釋放，阻止這一過(guò)程只會(huì)影響食欲信號(hào),，不會(huì)影響身體其他部位的細(xì)胞分解和儲(chǔ)存能量的使用,。
Singh稱，這一發(fā)現(xiàn)很可能可應(yīng)用于人類,，對(duì)治療肥胖癥有巨大的意義,。（生物谷 Bioon.com）
doi:10.1016/j.cmet.2011.06.008
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Autophagy in Hypothalamic AgRP Neurons Regulates Food Intake and Energy Balance
Susmita Kaushik1, 5, Jose Antonio Rodriguez-Navarro1, 5, Esperanza Arias1, 5, Roberta Kiffin1, 5, Srabani Sahu1, 3, Gary J. Schwartz1, 4, 6, Ana Maria Cuervo1, 2, 5, 6 and Rajat Singh
Macroautophagy is a lysosomal degradative pathway that maintains cellular homeostasis by turning over cellular components. Here we demonstrate a role for autophagy in hypothalamic agouti-related peptide (AgRP) neurons in the regulation of food intake and energy balance. We show that starvation-induced hypothalamic autophagy mobilizes neuron-intrinsic lipids to generate endogenous free fatty acids, which in turn regulate AgRP levels. The functional consequences of inhibiting autophagy are the failure to upregulate AgRP in response to starvation, and constitutive increases in hypothalamic levels of pro-opiomelanocortin and its cleavage product α-melanocyte-stimulating hormone that typically contribute to a lean phenotype. We propose a conceptual framework for considering how autophagy-regulated lipid metabolism within hypothalamic neurons may modulate neuropeptide levels to have immediate effects on food intake, as well as long-term effects on energy homeostasis. Regulation of hypothalamic autophagy could become an effective intervention in conditions such as obesity and the metabolic syndrome.
